Acute Sore Throat

Context

Sore throat accounted for 1.9% of all visits to emergency departments in the USA in 2006 (1). This figure represents a small percentage of the total disease prevalence as only about 15% of people with an upper respiratory tract infection seek medical care (2).

Most sore throats have an unknown or viral aetiology but group A haemolytic streptococcus (GABHS) is identified as the infecting agent in approximately 5 15% of all cases (3). GABHS infection may be complicated by significant sequelae such as rheumatic fever, peritonsillar abscess (quinsy) and post-streptococcal glomerulonephritis.

Even though the vast majority of patients with a sore throat have a benign, self-limiting course, one study found that 64% of primary care patients in the UK are prescribed antibiotics for a sore throat (4).

A recent Cochrane review showed that antibiotics give only modest symptomatic relief and only significantly reduce the risk of serious complications in areas where such complications e.g. rheumatic fever are common. (Spinks A, Glasziou PP, Del Mar CB. Antibiotics for sore throat. Cochrane Database Syst Rev 2013.updated)

Learning Bite

Although the minority of sore throats are caused by bacterial infection, almost 2/3 of patients are managed with a course of antibiotics.

Definition

Patients presenting with a sore throat are commonly diagnosed as having either pharyngitis or tonsillitis. However, it is more accurate to consider these diagnoses as part of a spectrum of a single disease process, tonsillopharyngitis, which encompasses infection or inflammation of the pharynx and/or tonsils.

Rarer, more serious problems such as peritonsillar abscess, epiglottitis and retropharyngeal abscess may also present with the symptom of a sore throat, and must be carefully differentiated from tonsillopharyngitis.

Learning Bite

Patients diagnosed with either tonsillitis or pharyngitis should be considered to have an illness which lies within the spectrum of tonsillopharyngitis.

Group A haemolytic streptococcus (streptococcus pyogenes) is the infective agent responsible for the most serious complications of tonsillopharyngitis.

The M protein GABHS is associated with diseases outside the pharynx, and it is the similarity of some of the serotypes to myocardial sarcolemma antigens that is responsible for the development of rheumatic fever in some patients.

A different process of antigen/antibody complex deposition in glomeruli is responsible for the development of post-streptococcal glomerulonephritis.

The image above provides the basic anatomy of the pharynx.

Exotoxins

GABHS may also release a variety of exotoxins which are responsible for illnesses such as toxic shock syndrome and necrotising fasciitis.

One of these exotoxins, streptolysin O, provokes a reliable immune response which can be measured via the antistreptolysin O titre (ASOT), a standard marker of GABHS infection.

Carriage rates

GABHS may be carried asymptomatically, maximally between the ages of 3 and 15, where carriage rates have been found between 5% and 21%. In adults, the rates are far lower, lying between 2.4% and 3.7% [5].

Complications

Untreated GABHS infection normally lasts between 8-10 days with patients remaining infectious during, and one week after, the illness. Complications of GABHS infection are categorised into suppurative and non-suppurative.

Suppurative complications

Suppurative complications such as otitis media, sinusitis and peritonsillar abscess arise from direct spread of infection into adjacent structures.

Non-suppurative complications

Non-suppurative complications are far rarer with the most common, rheumatic fever, having an annual incidence of less than 10 cases per 100,000 in western Europe and the USA [6].

However, 95% of new cases worldwide occur in the developing world(6) where rheumatic fever remains a significant problem and is responsible for approximately 500,000 deaths annually [7].

• Incidence of poststreptococcal glomerulonephritis (PSGN) 9 per 100 000 cases (Carapetis J. R., Steer A. C., Mulholland E. K., Weber M. The global burden of group A streptococcal diseases. The Lancet Infectious Diseases. 2005;5(11):685694.).
• Short term Prognosis; for Children Excellent, but 30% mortality in some particularly debilitated adults (Melby P. C., Musick W. D., Luger A. M., Khanna R. Poststreptococcal glomerulonephritis in the elderly. Report of a case and review of the literature. American Journal of Nephrology. 1987;7(3):235240.)
• Long term Children little difference in kidney function to normal population (Rodrguez-Iturbe B., Musser J. M. The current state of poststreptococcal glomerulonephritis. Journal of the American Society of Nephrology. 2008;19(10):18551864.).

Adults at 2 years, impaired renal function found in up to 30% of those affected (Pinto S. W., Sesso R., Vasconcelos E., Watanabe Y. J., Pansute A. M. Follow-up of patients with epidemic poststreptococcal glomerulonephritis. American Journal of Kidney Diseases. 2001;38(2):249255).

• In clinical practice, often only a single ASOT measurement is available and its timing in relation to a possible GAS infection is unknown. Interpretation of the result in this context is liable to misdiagnosis. In order to optimise diagnosis of preceding GAS infection, at least two sequential ASOT measurements, together with simultaneous assay for anti-DNase B, a second antistreptococcal antibody, is recommended

(Sen ES; Ramanan AV. How to use antistreptolysin O titres. Archives of Disease in Childhood Education & Practice. 99(6):231-8, 2014 Dec)

Learning Bite

Although rheumatic fever is a rare complication of GABHS infection in the western world, it remains a significant problem in the developing world.

History

In taking a history from a patient with a sore throat, the clinician must enquire about the course and duration of illness as well as other associated symptoms such as fever, headache and vomiting. In severe cases, the ability to swallow may be lost and lead to symptoms and signs of dehydration. Severe pain, neck stiffness or inability to swallow should also prompt the clinician to consider other more serious diagnoses such as epiglottitis and retropharyngeal abscess.

Abdominal symptoms such as pain and vomiting are common in children but the presence of gastrointestinal symptoms does not predict the presence of a streptococcal illness (8).
The patient must also be asked about previous non-suppurative complications of GABHS infection as there is an increased risk of both rheumatic fever and post-streptococcal glomerulonephritis with further GABHS infection.

Examination

An initial ABC assessment of the patient is important as it may indicate signs of airway obstruction, respiratory difficulty and circulatory collapse. These findings should prompt the junior clinician to seek experienced help immediately.

It is important to conduct a general examination of the patient as it may reveal;

• systemic features of infection such as fever and tachycardia
• heart murmurs found in rheumatic fever
• neck stiffness which may indicate lymphadenopathy or rarely, retropharyngeal abscess
• hepatosplenomegaly found in infectious mononucleosis
• rash which may be viral in origin but also consider;

An initial ABC assessment may indicate signs of airway obstruction, respiratory difficulty and circulatory collapse. These findings should prompt the junior clinician to seek experienced help immediately.

Signs of upper airway obstruction:

• Snoring
• Gurgling and/or pooling of saliva
• Stridor
• Hoarse voice
• In complete obstruction paradoxical chest movements

rheumatic fever erythema marginatum
scarlet fever a rough textured macular rash with confluence in the skin folds (Pastias lines) and red cheeks with perioral sparing

Sandpaper like rash of scarlet fever

Examination of the face and neck may identify suppurative complications of GABHS infection e.g. otitis media, mastoiditis, sinusitis. Lymphadenopathy in the neck is common in both viral and GABHS infection but the presence of conjunctivitis is more specifically associated with adenoviral infection.

Examination of the mouth and pharynx should be undertaken with care, in particular do not use a tongue depressor if there are any signs of potential airway obstruction as you may worsen the situation.

Learning Bite

Take care when examining the throat as over-vigorous examination or unnecessary painful procedures may worsen or precipitate airway obstruction.

Specific findings may include;

Palatal petechiae in GABHS infection

There are a number of red flag symptoms and signs that should prompt the clinician to consider a more serious cause for a sore throat, including;

• Significant systemic upset
• Severe pain
• Stridor
• Severe neck stiffness
• Inability to swallow / drooling of saliva
• Patient holding a tripod position

A patient with signs of potential or partial airway obstruction such as stridor, inability to swallow and holding a tripod position must be assessed urgently by a senior anaesthetist and otolaryngologist. In this situation the patient must not be moved unnecessarily or have any painful procedures undertaken, such as cannulation or blood gas sampling, until specialist support arrives.

Learning Bite

Patients with impending airway obstruction may present with a sore throat. A patient with stridor, inability to swallow or adopting a tripod position must be managed carefully and with senior anaesthetic and otolaryngology support.

To differentiate between viral causes and the potentially more serious GABHS infection, a number of tools have been developed to assess the probability of GABHS infection and therefore the need for antibiotic treatment. The most commonly cited score is that developed by Centor (9) and recently modified by McIsaac (10). This uses six variables to assess the likelihood of GABHS as the causative agent in sore throat;

History of fever or temperature > 38oC +1
Absence of cough +1
Tender anterior cervical lymphadenopathy +1
Tonsillar swelling or exudates +1
Age Age 45 years -1

The use of the sore throat score has been validated in an ED population and found to have a sensitivity of 97% and specificity of 78% (11). A comparison of its use against physician judgement in a primary care environment, resulted in a 50% reduction in antibiotics being prescribed (12).

Learning Bite

A sore throat score is useful in predicting the likelihood of GABHS infection and can reduce unnecessary antibiotic prescriptions by 50%.

Investigation Strategies:

There are a number of strategies that can be employed in the investigation of patients with a sore throat. In the USA and other countries without universal primary care backup, rapid streptococcal antigen testing has been widely utilised. The test is claimed to be 95% sensitive and specific but in some studies, sensitivity has varied between 55 and 90% and also has been found to vary considerably depending on the operator performing the test (12). In the only study carried out in an ED in the UK, rapid streptococcal antigen testing was found to have a sensitivity of 66% but 99% specificity (13). Amoxicillin and other Ampicillin antibiotics should be avoided in sore throat due to the possibility of causing maculopapular exanthems in patients with infectious mononucleosis.

Learning Bite

Rapid streptococcal antigen testing is very accurate at identifying GABHS infection but sensitivity is poor and experience in EDs in the UK is very limited.

A rising antistreptolysin O titre (ASOT) provides the gold standard criteria for immunologically significant GABHS infection. However it is impractical and unnecessary in the vast majority of cases. Throat swabs, although widely used, are reliant on correct technique and interpretation is complicated by asymptomatic carriers of GABHS.

Other investigations which may be useful in patients with a sore throat include;
Heterophile antibody tests for infectious mononucleosis e.g. Monospot and Paul Bunnell tests
Chest x ray if respiratory infection is suspected
Lateral soft tissue neck x ray for retropharyngeal abscess and epiglottitis
An epiglottic width (widest anteroposterior diameter of the epiglottis) of greater than 7mm was found to have a sensitivity and specificity of 100% for the diagnosis of epiglottitis in one study (14).

Epiglottic width indicated by arrow

Tonsillopharyngitis

The current recommended strategy for the management of uncomplicated tonsillopharyngitis in the UK relies on a pragmatic expectant policy i.e. no initial antibiotics are given and the patient is advised to return to their GP if their symptoms are not settling after a few days (15).

There are situations where antibiotic treatment is recommended for severe infection or high risk patients where there is:

• Marked systemic upset
• An increased risk of complications;
  Immunosuppressed patients e.g. diabetics or taking disease modifying anti-rheumatic drugs
  History of valvular heart disease
  History of rheumatic fever
• An outbreak of GABHS infection within an institution (e.g. barracks / boarding school)
• A history of repeated episodes of proven GABHS infection

This strategy is based on a Cochrane review of antibiotics for sore throat (16) which found that a course of antibiotics has minimal effect on the course of the illness, shortening it by approximately 16 hours. Another study found that an antibiotic prescription increases the chance of a patient with a sore throat returning in the future for antibiotics (17). Despite this evidence, antibiotic prescribing rates remain high. Patient expectation is often quoted as the main reason for this, but, in a study conducted in 10 EDs in the USA, patient satisfaction rates were not altered by the decision to prescribe antibiotics for upper respiratory tract infections (18).

Learning Bite

Treating an uncomplicated sore throat with antibiotics has little effect on the clinical course of the illness and may encourage patients to return in the future when a similar problem arises.

There is no doubt that antibiotics reduce the incidence of both suppurative and non-suppurative complications of GABHS infection. In the Cochrane review non-suppurative complications such as rheumatic fever were found to be reduced by antibiotic prescribing but this was only found in trials reporting before 1961 due to the extremely low incidence of rheumatic fever in the western world. Where the incidence of rheumatic fever remains high, such as in the developing world, antibiotics still have a significant role to play (16).
The incidence of glomerulonephritis was reported to be so small that no conclusions could be made. Use of a no antibiotic or delayed antibiotic strategy did not increase the incidence of complications in a study in primary care patients in the UK (17).

Where primary care follow up is lacking then it is reasonable to follow the USA guidance from the CDC which suggests that it is appropriate to use a no testing but use a clinical score based approach i.e. treat patients scoring 4 or 5 on the sore throat score (18).

Learning Bite

A strategy of expectant management is appropriate for most patients with an uncomplicated sore throat in the UK unless primary care follow up is lacking, where the decision to prescribe antibiotics should be based on a sore throat score.

If prescribing an antibiotic, phenoxymethylpenicillin is the standard agent recommended for a 10 day course. Phenoxymethylpenicillin is normally prescribed as a four times daily regime, although in a meta-analysis similar cure rates were found for twice daily dosing 19 with consequent better compliance rates.

In penicillin allergic patients, erythromycin or clarithromycin should be used but, as there is a higher incidence of resistance in GABHS (up to 30%), patients will need to be followed up more closely.

There are many other treatments which may be used in isolation or in combination with antibiotics in patients with a sore throat. These include non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol, pneumococcal vaccine and improved doctor-patient communication. A number of these have a demonstrably greater treatment effect than that produced by antibiotics alone (20).

Learning Bite

Simple non-antibiotic treatments such as NSAIDs and paracetamol are effective in patients with a sore throat and may have a greater positive effect than antibiotics alone.

Scarlet Fever

Scarlet fever is a GABHS exotoxin-mediated illness which occurs far more commonly in children. Other than standard antibiotic treatment for GABHS, consideration must also be made of hydration status and intravenous fluid rehydration may be required.

Strawberry tongue

Peritonsillar Abscess

Uncomplicated peritonsillar abscess may be managed in the ED although it is common practice for patients to be referred to an ear, nose and throat (ENT) specialist due to a lack of familiarity with treatment techniques. Both needle aspiration and incision and drainage techniques may be used employed and have been found to be equally effective (21). The clinician must be aware of the potential complications of both the problem e.g. Lemierres syndrome (extension of infection involving the jugular vein) and its management e.g. accidental puncture of the carotid artery.

Learning Bite

Peritonsillar abscess can be treated equally effectively by either needle aspiration or incision and drainage although the operator must be familiar with both the technique and the potential serious complications.

Epiglottitis

Since the advent of Hib vaccination, this is now more commonly an infection affecting adults. The main complication of airway obstruction may be predicted by the presence of specific clinical features (22);

• Stridor
• Muffled voice
• Rapid clinical course
• History of diabetes

A review of 106 patients with epiglottitis found that routine intubation was unnecessary as over 90% of patients recovered with a conservative watchful approach (23).

The main focus of treatment centres on observation for airway obstruction and administration of antibiotics a 3rd generation cephalosporin and metronidazole are recommended to cover the spectrum of organisms responsible.

Learning Bite

Since the advent of Hib immunisation, epiglottitis has become more common in adults and in the absence of high risk features, can normally be managed with antibiotics and careful observation.

Retropharyngeal Abscess

Although very uncommon, a combination of sore throat, fever, neck stiffness and stridor should alert the clinician to consider this diagnosis. Swelling or oedema of the posterior pharynx should prompt a consideration of advanced airway care and an urgent ENT opinion. Mortality rates are high when complications such as airway obstruction and mediastinitis arise.

• Sore throat is a common presentation to both the ED and primary care and is managed with an over-reliance on antibiotic prescription. (level of evidence 4)
• Non-suppurative complications of GABHS infection are extremely rare in the Western world, although in the developing world, rheumatic fever remains a very significant problem. (level of evidence 5)
• The presence of severe throat pain, stridor, significant systemic upset, neck stiffness, inability to swallow saliva and the patient holding a tripod position are all signs of a more serious cause for a sore throat. (level of evidence 5)
• Clinical features of partial or potential airway obstruction (stridor, altered voice, inability to swallow saliva, tripod position) must be managed by gentle handling of the patient and urgent senior ENT and anaesthetic assessment. (level of evidence 5)
• The sore throat score is a useful indicator of GABHS infection and can be used to guide investigation and management of patients where primary care follow-up is lacking. (level of evidence 2b)
• The treatment of uncomplicated sore throat with antibiotics has little effect on the course of the illness and the use of an expectant or delayed antibiotic policy does not increase the incidence of complications. (level of evidence 1a)
• Simple non-antibiotic treatments such as NSAIDs and paracetamol are effective and may have a larger treatment effect than antibiotics alone. (level of evidence 2a)
• In the absence of features associated with a high risk of airway obstruction, epiglottitis can normally be managed without routine intubation, using a strategy of intravenous antibiotics and close observation. (level of evidence 4)

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